What is the recommended surgical management for a patient with triple negative breast cancer and residual tumor after neoadjuvant therapy?

Surgical Management of Triple Negative Breast Cancer After Neoadjuvant Therapy with Residual Tumor

Primary Breast Surgery

For triple-negative breast cancer with residual disease after neoadjuvant chemotherapy, breast-conserving surgery with radiation is the preferred approach when adequate margins can be achieved, as it provides superior disease-free and overall survival compared to mastectomy. 1

Breast Surgery Options

• Breast-conserving surgery (BCS) plus radiation therapy is recommended when the residual tumor can be excised with negative margins, as retrospective analysis of 1,074 patients with early-stage node-negative TNBC demonstrated that BCS was associated with improved disease-free survival (HR 0.51, p<0.001) and overall survival (HR 0.43, p<0.001) compared to mastectomy 1

• Mastectomy should be performed when breast-conserving surgery cannot achieve adequate margins, for multifocal residual disease, or when the tumor reduction after neoadjuvant therapy is limited 2

• Breast MRI is the most accurate modality for assessing the extent of residual disease following neoadjuvant treatment and should guide surgical planning 2

Critical Surgical Planning Points

• The primary tumor site must be marked with a clip or carbon localization under ultrasound guidance before starting neoadjuvant therapy to facilitate accurate surgery, especially when breast conservation is anticipated 2

• Surgery should be scheduled 3-4 weeks after the final chemotherapy cycle to allow for count recovery 3

Axillary Surgery Management

Axillary lymph node dissection is required for any residual macrometastatic disease (>2mm) in sentinel lymph nodes after neoadjuvant chemotherapy, as 73% of the St. Gallen panel endorsed this approach due to substantial risk of additional nodal metastases. 2

Axillary Surgery Algorithm

For patients with clinically positive nodes after neoadjuvant therapy:

• Axillary lymph node dissection is mandatory 2

For patients who converted from cN1 to cN0 after neoadjuvant therapy:

• Sentinel lymph node biopsy is appropriate when the initially clipped node and at least three sentinel nodes can be identified and resected 2
• If no residual nodal disease is found, axillary dissection is not required 2

For patients with residual disease in sentinel nodes:

• Macrometastases (>2mm) in sentinel nodes: Completion axillary lymph node dissection is required, even if only one of three sentinel nodes is positive 2
• Micrometastases (<2mm): Controversial—axillary radiation may be considered as an alternative to dissection, though retrospective data show substantial risk of additional nodal metastases 2
• Isolated tumor cells only: Axillary radiation is a reasonable alternative to dissection 2

Important Axillary Management Caveats

• Real-world data from the National Cancer Database demonstrated lower survival when substituting sentinel node biopsy and regional nodal irradiation for axillary dissection when residual nodal disease is present, unless patients had limited residual nodal burden (only one positive node) and ER-positive tumors 2

• For triple-negative breast cancer specifically, the evidence supporting axillary radiation as an alternative to dissection in the setting of residual nodal disease is less robust than for ER-positive disease 2

Post-Surgical Systemic Therapy

Adjuvant capecitabine for 6-8 cycles should be offered to all patients with residual invasive disease after neoadjuvant chemotherapy who are germline BRCA1/2 wild-type, based on the CREATE-X trial demonstrating survival benefit. 2, 4, 5

Systemic Therapy Recommendations

• Capecitabine is the standard post-neoadjuvant adjuvant therapy for TNBC with residual disease 2

• For patients who received pembrolizumab during neoadjuvant therapy, adjuvant pembrolizumab should be continued to complete the full treatment course regardless of pathologic response 4, 5, 3

• For patients with germline BRCA1/2 mutations and residual disease, adjuvant olaparib for 1 year should be added after completion of chemotherapy and surgery 5

Radiation Therapy

Whole breast radiation therapy is mandatory after breast-conserving surgery, as it reduces the 10-year risk of any first recurrence by 15% and the 15-year risk of breast cancer-related mortality by 4%. 2

Radiation Therapy Guidelines

• Post-operative radiation therapy is strongly recommended after breast-conserving surgery 2, 4, 5

• Boost irradiation to the tumor bed provides an additional 50% relative risk reduction and is indicated for patients with unfavorable risk factors including age <50 years, grade 3 tumors, extensive DCIS, vascular invasion, or focally positive margins 2

• Post-mastectomy radiation therapy should be administered if positive lymph nodes are found at surgery, or if there are positive or close surgical margins 4, 5

• Radiation therapy should be given regardless of the decision regarding axillary dissection versus observation for lower-burden nodal disease 2

Common Pitfalls to Avoid

• Do not omit sentinel node biopsy or axillary staging in patients who converted to clinically node-negative status after neoadjuvant therapy—these patients still require pathologic assessment of the axilla 2

• Do not substitute axillary radiation for axillary dissection in triple-negative breast cancer patients with macrometastatic residual disease in sentinel nodes, as survival data support completion dissection in this population 2

• Do not withhold capecitabine in patients with residual disease based on concerns about tolerability—the CREATE-X trial demonstrated clear survival benefit that outweighs toxicity concerns 2

• Do not delay surgery excessively after completion of neoadjuvant chemotherapy—optimal timing is 3-4 weeks to allow count recovery while avoiding tumor regrowth 3